Nephron最新文献

Background: It sounds paradoxical that a tiny component of the cellular mantle known as glycocalyx is also the most ubiquitous, more so than mitochondria or nuclei, endowing glycocalyx coverage to every cell with no exceptions. Despite a relatively short history, this organelle has received exponentially growing attention and number of publications as reflected in the last decade. This cellular mantle consists of 4 transmembrane proteins and 6 GPI-anchored proteins, all of which are decorated with glycosaminoglycans like heparan, chondroitin and dermatan sulfates, and hyaluronic acid. All this has been exhaustively reviewed.

Summary: Our goal here will be to briefly sketch the important common features of glycocalyx, especially of endothelial cells, and to focus on clinically pertinent practical aspects of this structure. We will describe visual and biochemical detection challenges, highlight the usefulness of identifying and quantifying glycocalyx fragments in biological fluids while broadening the spectrum of specimens for diagnostic purposes, and discuss how these parameters may provide valuable clues regarding their therapeutic relevance as pharmacological targets.

Key message: The glycocalyx represents a clinically valuable target and advances in its detection can enhance diagnostic precision and strengthen its translational relevance.

Background: Chronic kidney disease (CKD) is a growing public health problem, resulting in significant morbidity and mortality. The relationship between air pollution (particulate matter (PM)2.5, PM2.5-10, and PM10, Nitrogen oxides (NOX), Nitrogen dioxide (NO2)) and kidney function has raised concerns. However, the causal relation remains uncertain. This study aimed to determine the impact of air pollution exposure on kidney function.

Methods: A two-sample Mendelian randomization (MR) study was launched using summary data from genome-wide association studies. Five MR methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode, were applied to investigate the potential causal relationship between air pollution exposure and kidney function, with the IVW method serving as the primary approach. MR-Egger regression, MR-PRESSO, and leave-one out analysis were used to strengthen the results.

Results: The MR analysis revealed a significant association between exposure to PM2.5-10 and an increased risk in CKD (OR:1.631; 95% confidence interval [CI] 1.161, 2.290), eGFRcrea (β: -0.013; 95% CI -0.021, -0.004), and eGFRcys (β: -0.024; 95% CI -0.039, -0.008). NOx was identified as a risk factor for eGFRcys (β: -0.016; 95% CI -0.029, -0.003). NO2 was associated with increased urine albumin-to-creatinine ratio (UACR) levels (β: 0.039; 95% CI 0.009, 0.069). However, no significant relationship was observed between PM2.5 or PM10 exposure and kidney function. No significant heterogeneity or horizontal pleiotropy was observed.

Conclusion: Our MR analysis reveals a genetic causal relation between air pollution especially PM2.5-10 and deteriorating kidney function, which may help provide new insights into further mechanisms and clinical studies in air pollution-mediated kidney diseases.

The kidney matrix, once viewed as a static scaffold, is now recognised as a dynamic microenvironment that undergoes continual remodelling in response to physiological cues. Emerging evidence demonstrates that this remodelling follows circadian patterns driven by molecular clocks within specific kidney cell types. This review synthesises recent advances on circadian regulation of the kidney matrisome, with emphasis on glomerular compartments. Circadian clocks in the glomerulus coordinate the timing of matrix turnover to preserve structural integrity, maintain filtration, and promote repair. Disruption of these rhythms contributes to maladaptive matrix accumulation, fibrosis, and kidney disease progression. Finally, we discuss mechanistic insights and translational opportunities, including chronotherapy and clock-targeted interventions. Understanding circadian control of glomerular matrix dynamics provides a framework for linking temporal biology to kidney health and disease.

Introduction Acadian variant Fanconi syndrome (AVFS) is an autosomal recessive disease caused by a mutation in the NDUFAF6 gene which results in mitochondrial dysfunction and oxidative damage to the kidneys. It presents as a slowly progressive chronic kidney disease and proximal tubular dysfunction that, in contrast to typical Fanconi Syndrome, leads to end-stage renal disease. It is diagnosed clinically and is present only in Acadian people. The objective of this study is to evaluate the effect of N-acetyl-L-cysteine (NAC), an antioxidant, on the progression of loss of renal function in patients with AVFS. Case Presentation Chart reviews were conducted on four active cases of AVFS not on kidney replacement therapy. Data on age, estimated glomerular filtration rate (eGFR), creatinine, medications and blood pressure were collected. Progression of eGFR was evaluated in each patient before and after NAC prescription, and the projected time to kidney replacement therapy (eGFR = 10 mL/min/1.73m2) with and without the use of NAC was calculated for each case. NAC had a positive effect on slowing the rate of eGFR loss in each patient. The projected need for kidney replacement therapy was delayed by an average of 9 years in the treated patients who otherwise would have required it by an estimated mean age of 28 years. Conclusion This study suggests that NAC has a beneficial effect on slowing the progression of kidney disease in patients with AVFS. This may be due to the modulation of oxidative stress by NAC. Further studies are needed to evaluate the potential benefits of NAC in other chronic kidney conditions.

Introduction: Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by pathogenic variants in the CFTR gene, leading to impaired chloride and bicarbonate transport across epithelial tissues. While typically diagnosed in infancy due to classic respiratory and gastrointestinal symptoms, atypical forms can present later in life with subtle or isolated manifestations. This case represents a rare monosymptomatic and atypical adult-onset presentation of cystic fibrosis, with electrolyte disturbances as the sole clinical manifestation.

Case presentation: We present the case of a 31-year-old man who developed recurrent episodes of profound electrolyte imbalance and acute kidney injury following intense physical activity in high environmental temperatures. He exhibited syncope, muscle cramps, and signs of severe dehydration. Laboratory tests revealed hyponatremia, hypokalemia, hypochloremia, hemoconcentration, and elevated creatinine levels, with urine findings consistent with extrarenal salt loss. A similar episode had occurred six years earlier. In the absence of an identifiable cause, CF was suspected. Sweat chloride testing confirmed the diagnosis in two separate samples. Genetic analysis revealed compound heterozygosity for a pathogenic CFTR variant and a variant of uncertain significance. Screening for other common manifestations of CF was negative.

Conclusion: This case underscores the diagnostic challenge of adult-onset CF, particularly in regions where neonatal screening was not historically implemented. Electrolyte disturbances, especially in the context of heat stress, may represent the only clinical clue in patients with residual CFTR function. Prompt recognition and diagnosis are essential for initiating appropriate monitoring and treatment, including the potential use of CFTR modulator therapies that can significantly improve quality of life and long-term outcomes.

Background: The determinants of glomerular filtration rate (GFR) and its changes over time are multiple and diverse. Nephron endowment is the starting point for GFR. Low renal endowment due to maternal undernutrition or premature birth as well as the loss of renal mass because of surgical procedures have a major impact of GFR Eventually low renal mass may lead to organ damage when combined with metabolic syndrome and obesity or diabetes. The kidney has a major role in maintaining homeostasis. Changes in metabolic demand have a major influence in renal function. Increments in metabolic demand may determine a compensatory increase in GFR to cope with the new metabolic status. Clear examples of these conditions are pregnancy and obesity. Also, GFR may vary in response to the stimulation of renal reserve and the ageing process. All these aspects are different in men and women and may explain gender differences in renal function in health and disease.

Summary: In general, women have lower renal mass and lower metabolic demand. However, the study of these aspects in humans is complex. A living donor has two healthy kidneys and after nephrectomy, one of them remains in the same subject undergoing mechanisms of compensation whereas the other is transplanted in a patient with CKD that might have different body size, sex or age, than the donor. This makes the living kidney donation a unique setting to study the determinants of GFR. In this review, we take advantage of data from living kidney donors and recipients to understand diverse determinants of GFR, focusing on gender differences in renal function.

Key messages: In health and disease, several factors influence GFR like renal mass, the presence or absence of renal reserve, metabolic demand, the capacity of the kidney to adapt to it and the effect of ageing and senescence. In all of them, gender differences play a relevant role, making differences between men and women a factor to consider in the analysis of GFR.

Objective: Explore the positive rate of anti-nephrin antibodies in various podocytopathies and their relationship with the clinical characteristics and outcomes of podocytopathies.

Methods: Medical literatures from the Pubmed database and the Web of science database from the establishment of the databases to July 28, 2025 were retrieved online. The main exploration indicator is the positive rate of anti-nephrin antibody in podocytopathies. Other indicators include the diagnostic role of anti-nephrin antibodies and their relationship with the clinical features and outcomes of podocytopathies. Analysis was conducted using the R software package 'Meta' and 'Mada'.

Results: A meta-analysis included a total of 1,567 patients from 15 studies. The positive rates of anti-nephrin antibodies in adult patients with primary podocytopathies, minimal change disease (MCD), primary focal segmental glomerulosclerosis (pFSGS), and children with idiopathic nephrotic syndrome (INS) were 41% and 51%, 32%, and 39%, respectively. Anti-nephrin antibodies are almost undetectable in patients with secondary FSGS, membranous nephropathy and other glomerular diseases. In podocytopathies with nephrotic-range proteinuria or without the use of immunosuppressants, the positive rate increased. The sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of anti-nephrin antibody in differentiating steroid-sensitive NS(SSNS) from non-SSNS in children were 0.57, 0.83, and 3.40 and 0.55, respectively. Patients positive for anti-nephrin antibody had higher urinary protein levels and lower serum albumin levels, more prone to recurrence, but there were no statistically significant differences in gender, age, renal function, and remission rate. The heterogeneity of the positive rate results of anti-nephrin antibodies in the literature is very high (I2>80%), and most subgroup analyses cannot explore the source of the heterogeneity.

Conclusion: Anti-nephrin antibodies have a relatively high positive rate in podocytopathies and have a differentiating effect on SSNS and non-SSNS in children. Anti-nephrin antibodies are associated with the clinical severity and recurrence of podocytopathies.

Introduction: The utility of M-type phospholipase A2 receptor antibody (PLA2R-Ab) for risk stratification in membranous nephropathy (MN) remains suboptimal, while soluble T-cell immunoglobulin and mucin-domain containing-3 (sTim-3) has been confirmed as a critical immune regulator in kidney diseases. This study investigated the prognostic value of sTim-3 in PLA2R-associated MN (PMN) and the efficacy of its combination with PLA2R-Ab.

Methods: Serum PLA2R-Ab and sTim-3 levels were measured at baseline in 50 PMN patients using highly sensitive time-resolved fluorescence immunoassay (TRFIA) method. Patients were stratified into complete remission, partial remission, and no remission (NR) groups according to 12-month treatment outcomes.

Results: Prognostic cut-off discriminating NR from remission: sTim-3 = 17.63 ng/mL; PLA2R-Ab = 50 RU/mL (KDIGO high-risk threshold). The non-remission rate for patients with PLA2R-Ab <50 RU/mL was 23.58%, whereas the sTim-3 + PLA2R-Ab combination achieved 0%. Among 16 "high-risk" patients (PLA2R-Ab >50 RU/mL), sTim-3 demonstrated 93.75% accuracy in predicting outcomes. Remarkably, all 8 patients who achieved actual remission exhibited sTim-3 levels below 17.63 ng/mL. Double positivity (PLA2R-Ab >50 RU/mL and sTim-3 >17.63 ng/mL) identified a refractory subgroup with significantly poorer treatment response compared to other groups.

Conclusion: sTim-3 serves as a complementary biomarker to PLA2R-Ab. Combined detection optimizes PMN risk stratification: PLA2R-Ab >50 RU/mL and sTim-3 >17.63 ng/mL indicates an immune-activated state requiring intensive immunosuppression, preventing overtreatment in PLA2R-Ab-high patients with favorable immune status.

Introduction: L-Glutamine is increasingly used as a dietary supplement and its use is, as is the case with other amino acids, considered safe. L-Glutamine is the most abundant amino acid in the human body and is involved in many metabolic reactions. Within the kidney L-glutamine has an important role in the generation of ammonia and bicarbonate.

Case presentation: We report a case of acute kidney injury (AKI) as a result of tubular damage in a patient who used 18 grams of L-glutamine on a daily basis. Possible mechanisms are proposed of which increased single nephron ammonia production and toxicity seems most likely cause of AKI.

Conclusion: We advise cautious use of L-glutamine supplements in elderly patient with an already compromised kidney function.

Background: Diabetic kidney disease (DKD) is a serious complication arising from long-term diabetes, disproportionately affecting historically marginalized populations, such as racial and ethnic minority groups, populations with low socioeconomic status, or a lower level of education. This review explores the causes of these disparities and barriers to accessing DKD therapies and proposes solutions. Summary: Socioeconomic factors like lack of health insurance, low income, and limited health literacy significantly hinder access to DKD therapies for marginalized communities. Additionally, inadequate access to healthcare services further exacerbates the issue. Clinical factors also contribute to the inequity. Under-recognition of DKD, under-prescription of effective medications, and a lack of a patient-centered healthcare environment are prominent concerns. Implicit bias among healthcare professionals may also play a role. Patient factors include limited awareness of DKD, challenges with treatment adherence, and frequent healthcare interruptions. Policy interventions like the Inflation Reduction Act, expanding health insurance coverage, and increasing reimbursement for DKD therapies can improve affordability and access. Additionally, a shift toward preventive care models is crucial. Clinical interventions focus on improving early detection, accurate diagnosis, and proper management of DKD. Educating healthcare providers about the benefits of DKD therapies and implementing value-based kidney care programs are essential steps. Patient interventions involve raising awareness about DKD, implementing culturally appropriate educational programs, and fostering community-based support systems. Key Messages: Addressing these disparities requires a multipronged approach involving policy changes, improved healthcare delivery, and patient education. This collaborative effort can ensure equitable access to DKD therapies and improve health outcomes for all populations.